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Potential bile acid metabolites. 24. An efficient synthesis of carboxyl-linked glucosides and their chemical properties

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Lipids

Abstract

A facile and efficient synthesis of the carboxyl-linked glucosides of bile acids is described. Direct esterification of unprotected bile acids with 2,3,4,6-tetra-O-benzyl-d-glucopyranose in pyridine in the presence of 2-chloro-1,3,5-trinitrobenzene as a coupling agent afforded a mixture of the α- and β-anomers (ca. 1∶3) of the 1-O-acyl-d-glucoside benzyl ethers of bile acids, which was separated effectively on a C18 reversedphase chromatography column (isolated yields of α- and β-anomers are 4–9% and 12–19%, respectively). Subsequent hydrogenolysis of the α- and β-acyl glucoside benzyl ethers on a 10% Pd−C catalyst in acetic acid/methanol/EtOAc (1∶2∶2, by vol) at 35°C under atmospheric pressure gave the corresponding free esters in good yields (79–89%). Chemical specificities such as facile hydrolysis and transesterification of the acyl glucosides in various solvents were also discussed.

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Abbreviations

CA:

cholic acid

CDCA:

chenodeoxycholic acid

CTNB:

2-chloro-1,3,5-trinitrobenzene

DCA:

deoxycholic acid

ESI:

electrospray ionization

FT:

Fourier transform

HDCA:

hyodeoxycholic acid

HR-MS:

high-resolution mass spectra

IR:

inrrared

LCA:

lithocholic acid

MDCA:

murideoxycholic acid

NIM:

negative ion mode

NMR:

nuclear magnetic resonance

mp:

melting points

PIM:

positive ion mode

TBGP:

2,3,4,6-tetra-O-benzyl-d-glucopyranose

UDCA:

ursodeoxycholic acid

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Authors and Affiliations

  1. Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajousui, Setagaya, 156-8550, Tokyo, Japan

    Takashi Iida, Ryusei Nakamori, Rie Yabuta, Satoru Yada & Yuzuru Takagi

  2. Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, 981-8578, Sendai, Japan

    Nariyasu Mano, Shigeo Ikegawa & Junichi Goto

  3. Hoshi University, Shinagawa, Ebara, 147-8501, Tokyo, Japan

    Toshio Nambara

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  1. Takashi Iida
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  2. Ryusei Nakamori
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Correspondence to Takashi Iida.

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Iida, T., Nakamori, R., Yabuta, R. et al. Potential bile acid metabolites. 24. An efficient synthesis of carboxyl-linked glucosides and their chemical properties. Lipids 37, 101–110 (2002). https://doi.org/10.1007/s11745-002-0869-3

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  • DOI: https://doi.org/10.1007/s11745-002-0869-3

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